From:  "Vijay V. Upreti" vupre001@umaryland.edu
Subject: [NMusers] dose compartment 
Date: Wed, March 30, 2005 11:35 pm 

Dear all,

I have data from a PK study with small number of subjects, which were given 
an IV bolus dose followed by IM administration with a washout period in 
between. I wish to fit this data simultaneously. I have doubt regarding, 
assigning the dosing compartment for IM administration.

I do understand that each NONMEM, PK model has a default dose compartment 
and CMT can be used in the data item, to specify dosing in any compartment 
other than default, but I am wondering whether the IM dose should be 
assigned to the DEPOT or to the PERIPHERAL compartment.

Referring to the NONMEM user guide part V, chapter 6, section 8.2.1, page 
58, it says an IM injection can be considered as dose to peripheral 
compartment, I am wondering if one wishes to use a mono exponential decline 
model like ADVAN2, to fit IM data like this, than by default there is no 
peripheral compartment. My question specifically is what should be the 
appropriate compartment for assigning IM dose, depot or peripheral.

I have another issue, may be because of delayed sampling time points, I can 
not see a absorption phase in the IM data and it looks very much similar to 
IV data, with the first sampling point being Cmax, further the 
bioavailability > 100 %. In such a case what should be the ideal way to 
model this data 1. Fix KA based on literature reports or 2. To ignore 
absorption and model this data just like IV dosing with dose input directly 
to central compartment. I do not know if this is an appropriate example but 
in the NONMEM user guide part V, chapter 2, section 3.2, page 13 for a 
similar situation like this, where time points after oral dosing were 
delayed and absorption was assumed to be complete, (ADVAN 1) one compartment 
model, without first order absorption was considered complete.
Kindly provide your thoughts, and forgive me for this long email.

Thanks in advance.

_______________ 
Vijay V Upreti
Graduate Student
Pharmacokinetics-Biopharmaceutics Laboratory 
Department of Pharmaceutical Sciences
University of Maryland, School of Pharmacy 
20 Penn St., Baltimore, MD 21201 
Voice: 410-706-7388 
Fax: 410-706-5017
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From: "Bhattaram, Atul" BhattaramA@cder.fda.gov
Subject:  RE: [NMusers] dose compartment
Date:  Thu, March 31, 2005 10:26 am 

Hello Vijay

You can use the dosing compartment for IM administration similar to oral
administration. You can either fix Ka to the literature value or try
different values of Ka to see how it affects your analysis.

Venkatesh Atul Bhattaram
Pharmacometrics
DPE-1, OCPB
CDER, FDA.
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